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PMID: 9114034 Published · ppublish English Comparative Study Journal Article Research Support, U.S. Gov't, P.H.S.

A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 9 ·1997-04-29 ·Pages 4587-92

Hansen RS, Canfield TK, Fjeld AD, Mumm S, Laird CD, Gartler SM

Abstract

The timing of DNA replication in the Xq27 portion of the human X chromosome was studied in cells derived from normal and fragile X males to further characterize the replication delay on fragile X chromosomes. By examining a number of sequence-tagged sites (STSs) that span several megabases of Xq27, we found this portion of the normal active X chromosome to be composed of two large zones with different replication times in fibroblasts, lymphocytes, and lymphoblastoid cells. The centromere-proximal zone replicates very late in S, whereas the distal zone normally replicates somewhat earlier and contains FMR1, the gene responsible for fragile X syndrome when mutated. Our analysis of the region of delayed replication in fragile X cells indicates that it extends at least 400 kb 5' of FMR1 and appears to merge with the normal zone of very late replication in proximal Xq27. The distal border of delayed replication varies among different fragile X males, thereby defining three replicon-sized domains that can be affected in fragile X syndrome. The distal boundary of the largest region of delayed replication is located between 350 and 600 kb 3' of FMR1. This example of variable spreading of late replication into multiple replicons in fragile X provides a model for the spread of inactivation associated with position-effect variegation or X chromosome inactivation.

MeSH Terms
Cell Cycle DNA Replication DNA, Complementary/genetics Dosage Compensation, Genetic Fibroblasts/cytology Fragile X Mental Retardation Protein Fragile X Syndrome/genetics Gene Expression Genetic Markers Hematopoietic Stem Cells/cytology Humans Lymphocytes/cytology Male Nerve Tissue Proteins/genetics RNA-Binding Proteins Time Factors X Chromosome/genetics
Chemicals
DNA, Complementary FMR1 protein, human Genetic Markers Nerve Tissue Proteins RNA-Binding Proteins Fragile X Mental Retardation Protein
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hansen R S
Department of Medicine, University of Washington, Seattle, WA 98195, USA. shansen@genetics.washington.edu
Canfield T K
Fjeld A D
Mumm S
Laird C D
Gartler S M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.9.4587
Email
shansen@genetics.washington.edu
Published
1997-04-29
Pages
4587-92
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC20767
Subset
IM
Grants
NIGMS NIH HHS · R01 GM053805 · United States
NICHD NIH HHS · R01 HD016659 · United States
NIGMS NIH HHS · GM53805 · United States
NICHD NIH HHS · HD16659 · United States
External Links
PubMed source DOI: 10.1073/pnas.94.9.4587 PMC Full Text View journal details
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